NM_007373.4(SHOC2):c.1594A>G (p.Ser532Gly) AND not specified

Germline classification:: Benign (3 submissions)
Last evaluated:: Feb 17, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000128044.7

Allele description [Variation Report for NM_007373.4(SHOC2):c.1594A>G (p.Ser532Gly)]

NM_007373.4(SHOC2):c.1594A>G (p.Ser532Gly)

Gene:

SHOC2:SHOC2 leucine rich repeat scaffold protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q25.2

Genomic location:

Preferred name:

NM_007373.4(SHOC2):c.1594A>G (p.Ser532Gly)

Other names:

p.S532G:AGC>GGC; NM_007373.3(SHOC2):c.1594A>G

HGVS:

NC_000010.11:g.111011663A>G
NG_028922.1:g.97121A>G
NM_001269039.3:c.1456A>G
NM_001324336.2:c.1594A>G
NM_001324337.2:c.1594A>G
NM_007373.4:c.1594A>GMANE SELECT
NP_001255968.1:p.Ser486Gly
NP_001311265.1:p.Ser532Gly
NP_001311266.1:p.Ser532Gly
NP_031399.2:p.Ser532Gly
NP_031399.2:p.Ser532Gly
LRG_753t1:c.1594A>G
LRG_753:g.97121A>G
LRG_753p1:p.Ser532Gly
NC_000010.10:g.112771421A>G
NM_007373.3:c.1594A>G
NR_136749.2:n.945A>G

Protein change:

S486G

Links:

dbSNP: rs145463534

NCBI 1000 Genomes Browser:

rs145463534

Molecular consequence:

NM_001269039.3:c.1456A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324336.2:c.1594A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001324337.2:c.1594A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007373.4:c.1594A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136749.2:n.945A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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lysosomal acid lipase/cholesteryl ester hydrolase isoform X1 [Homo sapiens]
lysosomal acid lipase/cholesteryl ester hydrolase isoform X1 [Homo sapiens]
gi|2462519347|ref|XP_054221916.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000171635	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Oct 22, 2013)	germline	clinical testing	Citation Link,
SCV000311807	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001338168	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Feb 17, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000171635

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Oct 22, 2013)

germline

clinical testing

Citation Link,

SCV000311807

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001338168

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Feb 17, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000171635.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000311807.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001338168.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: SHOC2 c.1594A>G (p.Ser532Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 282828 control chromosomes, predominantly at a frequency of 0.013 within the African or African-American subpopulation in the gnomAD database, including 3 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 520 fold of the estimated maximal expected allele frequency for a pathogenic variant in SHOC2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. In addition, one expert panel, ClinGen RASopathy Variant Curation Expert Panel, classified this variant as benign after 2014. Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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